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Antibiotic Efficacy Testing in an Ex vivo Model of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms in the Cystic Fibrosis Lung
Published on: January 22, 2021
Effect of clarithromycin in experimental empyema by multidrug-resistant Pseudomonas aeruginosa
Eirini-Charikleia Tsovolou1, Ira-Maria Tzepi, Aikaterini Spyridaki
14th Department of Internal Medicine, Medical School, University of Athens, Athens, Greece.
Abstract:
Evidence from a recent randomized study of our group suggests that intravenous clarithromycin resulted in earlier resolution of ventilator-associated pneumonia. The need to understand the mechanism of action of clarithromycin guided to the study of a model of experimental empyema by multidrug-resistant Pseudomonas aeruginosa in 40 rabbits. Animals were randomized into controls (group A); treatment with clarithromycin (group B); treatment with piperacillin/tazobactam (group C); and treatment with both agents (group D). Pleural fluid was collected at regular time intervals for quantitative culture, estimation of cell apoptosis and of concentrations of tumour necrosis factor-alpha (TNFα). After 7 days, animals were euthanized for estimation of tissue growth. Bacterial growth in the pleural fluid of group D was significantly decreased compared with the other groups on day 5. Lung growth of group D was lower than group A. That was also the case of cytokine stimulation by pleural fluid samples on U937 monocytes. It is concluded that administration of clarithromycin enhanced the antimicrobial efficacy of piperacillin/tazobactam and decreased bacterial growth in the pleural fluid and in tissues. It also attenuated the pro-inflammatory phenomena induced by the β-lactam.
Insights
Clarithromycin combined with piperacillin/tazobactam significantly reduced bacterial growth and inflammation in experimental empyema. This combination therapy offers enhanced efficacy for treating multidrug-resistant Pseudomonas aeruginosa infections.
Area of Science:
- Infectious Diseases
- Pharmacology
- Experimental Medicine
Background:
- Ventilator-associated pneumonia (VAP) treatment can be challenging, particularly with multidrug-resistant pathogens.
- Intravenous clarithromycin has shown promise in accelerating VAP resolution.
- Understanding the mechanism of clarithromycin's action is crucial for optimizing treatment strategies.
Purpose of the Study:
- To investigate the synergistic effect of clarithromycin and piperacillin/tazobactam in a rabbit model of empyema.
- To elucidate the impact of this combination therapy on bacterial load, inflammation, and tissue damage.
Main Methods:
- An experimental empyema model was established in 40 rabbits using multidrug-resistant Pseudomonas aeruginosa.
- Animals were randomized into four groups: control, clarithromycin alone, piperacillin/tazobactam alone, and combination therapy.
- Pleural fluid and tissue samples were analyzed for bacterial culture, apoptosis, tumor necrosis factor-alpha (TNFα) levels, and tissue growth.
Main Results:
- Combination therapy (clarithromycin + piperacillin/tazobactam) significantly reduced pleural fluid bacterial growth by day 5 compared to monotherapy or control groups.
- Lung tissue growth was significantly lower in the combination therapy group compared to the control group.
- Pleural fluid from the combination group showed reduced pro-inflammatory cytokine stimulation (TNFα) in U937 monocyte assays.
Conclusions:
- Clarithromycin enhances the antimicrobial efficacy of piperacillin/tazobactam against multidrug-resistant Pseudomonas aeruginosa in empyema.
- The combination therapy effectively reduces bacterial burden and attenuates pro-inflammatory responses, suggesting a beneficial synergistic mechanism.
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